A deeper evaluation of cytokeratin fragment 21-1 as a lung cancer tumor marker and comparison of different assays

Studies show CYFRA 21-1 fragments of cytokeratin 19 (CK19) to be promising biomarkers for non-small cell lung cancer (NSCLC). Although previous literature identifies specific CYFRA 21-1 antibody binding epitopes, the exact molecular weight of the CK19 fragment being detected by current assays is not...

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Main Authors: Dianna J. Rowe, Timothy A. Khalil, Michael N. Kammer, Caroline M. Godfrey, Yong Zou, Cindy L. Vnencak-Jones, David Xiao, Stephen Deppen, Eric L. Grogan
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Biosensors and Bioelectronics: X
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590137025000202
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author Dianna J. Rowe
Timothy A. Khalil
Michael N. Kammer
Caroline M. Godfrey
Yong Zou
Cindy L. Vnencak-Jones
David Xiao
Stephen Deppen
Eric L. Grogan
author_facet Dianna J. Rowe
Timothy A. Khalil
Michael N. Kammer
Caroline M. Godfrey
Yong Zou
Cindy L. Vnencak-Jones
David Xiao
Stephen Deppen
Eric L. Grogan
author_sort Dianna J. Rowe
collection DOAJ
description Studies show CYFRA 21-1 fragments of cytokeratin 19 (CK19) to be promising biomarkers for non-small cell lung cancer (NSCLC). Although previous literature identifies specific CYFRA 21-1 antibody binding epitopes, the exact molecular weight of the CK19 fragment being detected by current assays is not well-documented. Serum samples from 58 patients (lung cancer (N = 36), control (N = 22)) were used to measure CYFRA 21-1 across four different quantification assays: enzyme-linked immunosorbent assay (ELISA), chemiluminescent assay (ChLIA), electrochemiluminescence immunoassay (ECLIA), and compensated interferometric reader (CIR). In the cancer group, correlation between ECLIA and ELISA was high (R(Pearson) = 0.948, r(Spearman) = 0.868) while correlation between ECLIA vs ChLIA and ECLIA vs CIR was low (R= 0.005, r = −0.0593), (R = 0.0275, r = 0.167), respectively. In the control group, correlation between ECLIA and ELISA was high (R = 0.948, r = 0.868) while correlation between ECLIA vs ChLIA and ECLIA vs CIR was low (R = 0.005, r = −0.0593), (R = 0.0275, r = 0.167), respectively. Compared to ECLIA, concordance coefficients (pc) were poor (pc < 0.90) across all assays except for cancers group in ELISA (pc = 0.913). ECLIA was the only assay to report control ranges above 1 ng/mL CYFRA 21-1 (ECLIA, 1.14–21.59 ng/mL; ELISA, 0.79–24.26 ng/mL; ChLIA, 0.062–0.691 ng/mL; 0.08–7.68 ng/mL). Differing sizes of the protein being measured by each assay may have a role in the discrepancies observed. Given the different CYFRA 21-1 concentration estimates among assays, further characterization of the fragment and its release during epithelial malignancies, such as NSCLC, is imperative to developing effective biomarker assays.
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spelling doaj-art-47da70fd43c64ac89bf99d59dd8d7a542025-08-20T02:06:44ZengElsevierBiosensors and Bioelectronics: X2590-13702025-05-012310059310.1016/j.biosx.2025.100593A deeper evaluation of cytokeratin fragment 21-1 as a lung cancer tumor marker and comparison of different assaysDianna J. Rowe0Timothy A. Khalil1Michael N. Kammer2Caroline M. Godfrey3Yong Zou4Cindy L. Vnencak-Jones5David Xiao6Stephen Deppen7Eric L. Grogan8Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN, USATennessee Valley Healthcare Systems, Nashville Campus, Nashville, TN, USA; Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA; Corresponding author. Tennessee Valley Healthcare Systems, Nashville Campus, Nashville, TN, USA.Studies show CYFRA 21-1 fragments of cytokeratin 19 (CK19) to be promising biomarkers for non-small cell lung cancer (NSCLC). Although previous literature identifies specific CYFRA 21-1 antibody binding epitopes, the exact molecular weight of the CK19 fragment being detected by current assays is not well-documented. Serum samples from 58 patients (lung cancer (N = 36), control (N = 22)) were used to measure CYFRA 21-1 across four different quantification assays: enzyme-linked immunosorbent assay (ELISA), chemiluminescent assay (ChLIA), electrochemiluminescence immunoassay (ECLIA), and compensated interferometric reader (CIR). In the cancer group, correlation between ECLIA and ELISA was high (R(Pearson) = 0.948, r(Spearman) = 0.868) while correlation between ECLIA vs ChLIA and ECLIA vs CIR was low (R= 0.005, r = −0.0593), (R = 0.0275, r = 0.167), respectively. In the control group, correlation between ECLIA and ELISA was high (R = 0.948, r = 0.868) while correlation between ECLIA vs ChLIA and ECLIA vs CIR was low (R = 0.005, r = −0.0593), (R = 0.0275, r = 0.167), respectively. Compared to ECLIA, concordance coefficients (pc) were poor (pc < 0.90) across all assays except for cancers group in ELISA (pc = 0.913). ECLIA was the only assay to report control ranges above 1 ng/mL CYFRA 21-1 (ECLIA, 1.14–21.59 ng/mL; ELISA, 0.79–24.26 ng/mL; ChLIA, 0.062–0.691 ng/mL; 0.08–7.68 ng/mL). Differing sizes of the protein being measured by each assay may have a role in the discrepancies observed. Given the different CYFRA 21-1 concentration estimates among assays, further characterization of the fragment and its release during epithelial malignancies, such as NSCLC, is imperative to developing effective biomarker assays.http://www.sciencedirect.com/science/article/pii/S2590137025000202CYFRA 21-1BiomarkerEnzyme-linked immunosorbent assay (ELISA)Chemiluminescent assay (ChLIA)Electrochemiluminescence immunoassay (ECLIA)Compensated interferometric reader (CIR)
spellingShingle Dianna J. Rowe
Timothy A. Khalil
Michael N. Kammer
Caroline M. Godfrey
Yong Zou
Cindy L. Vnencak-Jones
David Xiao
Stephen Deppen
Eric L. Grogan
A deeper evaluation of cytokeratin fragment 21-1 as a lung cancer tumor marker and comparison of different assays
Biosensors and Bioelectronics: X
CYFRA 21-1
Biomarker
Enzyme-linked immunosorbent assay (ELISA)
Chemiluminescent assay (ChLIA)
Electrochemiluminescence immunoassay (ECLIA)
Compensated interferometric reader (CIR)
title A deeper evaluation of cytokeratin fragment 21-1 as a lung cancer tumor marker and comparison of different assays
title_full A deeper evaluation of cytokeratin fragment 21-1 as a lung cancer tumor marker and comparison of different assays
title_fullStr A deeper evaluation of cytokeratin fragment 21-1 as a lung cancer tumor marker and comparison of different assays
title_full_unstemmed A deeper evaluation of cytokeratin fragment 21-1 as a lung cancer tumor marker and comparison of different assays
title_short A deeper evaluation of cytokeratin fragment 21-1 as a lung cancer tumor marker and comparison of different assays
title_sort deeper evaluation of cytokeratin fragment 21 1 as a lung cancer tumor marker and comparison of different assays
topic CYFRA 21-1
Biomarker
Enzyme-linked immunosorbent assay (ELISA)
Chemiluminescent assay (ChLIA)
Electrochemiluminescence immunoassay (ECLIA)
Compensated interferometric reader (CIR)
url http://www.sciencedirect.com/science/article/pii/S2590137025000202
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